Previous studies demonstrate that chiral biointerface has gr

Previous studies demonstrate that chiral biointerface has great influence on cells adhesion and proteins adsorption [39], [40], [41], [42], [43], which inspired us to further develop antimicrobial materials or surfaces by taking advantage of the “chiral taste” of microbes. L-borneol is a hydrophobic bicyclic monoterpene [44], and widely used as a safe and natural medical molecule [45]. Recently, our group revealed that borneol-based polymers [46], [47] or borneol-grafted cellulose [48] have unique antimicrobial adhesion properties by dramatically reducing microbial attachment and biofilm formation. Thus, we deduced that borneol-grafting was an effective strategy for endowing antifungal activity to solid graphene. Herein, we present a GO-borneol (denote as GOB) composite synthesized by esterification of borneol with thiomalic-acid-modified GO sheets, of which thiomalic OTX-015 is used as the linker molecule to increase surface carboxyl groups (Scheme 1). The covalent banding between GO and borneol prevents the shedding of borneol and gives a long-term antifungal effect to the GOB composite. With this modification, both antifungal activity and cytotoxicity of the GOB could be optimized compared with those of GMs, thus suggesting the GOB is a promising antifungal composite.
Experimental
Results and discussions
Conclusions In summary, we developed a novel graphene-based antifungal material GOB by esterification of borneol with thiomalic-acid-modified GO sheets. With a modified density of 23.8wt% of borneol, the antifungal activity of the GOB displays a dramatically conversion from GO’s affinity to distinct antifungal adhesion and growth inhibition. Deeply insight revealed that the carbon stereochemistry of the GOB was essential for this powerful antifungal performance. The covalent banding between GO and borneol molecules ensured its safe and long-term antifungal characteristic. Cytotoxicity assay also highlighted biocompatibility of the GOB. Thus, we believe that this work not only develops new strategies to control fungi adhesion, but also presents a new understanding of the GMs for advancing potential applications in antifungal fields.
Acknowledgements The authors thank the National Natural Science Foundation of China (21574008), and the Fundamental Research Funds for Central Universities (PYBZ1709, XK1701) for their funding support.
Key points
Introduction The early diagnosis of systemic fungal diseases in birds, especially aspergillosis, remains challenging because the clinical signs are usually nonspecific and there still is no single reliable noninvasive diagnostic test available in birds. Consequently, antifungal therapy is frequently administered empirically for presumptive invasive fungal infections in these patients without a definitive diagnosis being made. However, different factors need to be considered in the rational drug selection of antifungal therapy. First, the selected antifungal drug must be able to penetrate the center of infection in a concentration to which the fungus is susceptible. However, fungi, in contrast with bacteria, are eukaryotes, and consequently most antifungal agents are also toxic to the eukaryotic host cells. Therefore, taking into account their (often narrow) therapeutic index, no perfect antifungal agent exists. Nevertheless, in the last decades, newer and less toxic antifungals, including the azoles and echinocandins, have been developed for use in human medicine. Aside from the chemical structure, the impact of antifungal drug formulation and route of administration on treatment safety and efficacy have been investigated as well. Because knowledge of avian antifungal treatment is limited, treatment protocols are often developed empirically, based on case reports, or extrapolated from humans or other animal species. Because of the narrow therapeutic index, the dosing of antifungal drugs should be done carefully, with dose extrapolation preferably based on more advanced allometric and physiologically based pharmacokinetic (PK) modeling. In avian medicine, different antifungal agents are being used, but most of these substances have not been approved for administration in birds. However, recently (2014) the first antifungal product (itraconazole 10 mg/mL oral solution; Fungitraxx, Avimedical, Hengelo, The Netherlands) was registered for ornamental birds in Europe (EMA/698698/2013). The purpose of this review is to describe the interrelation of antifungal drug formulation, administration route, therapeutic–toxic range, and treatment outcome in fungal diseases, with a particular emphasis on aspergillosis in companion birds.